Innate local response and tissue recovery following application of high density microarray patches to human skin

David A Muller,Joakim Henricson,Chris D Anderson,Totte Togö,Pierre A Lemaire,Angus Forster,Cesar M Jayashi Flores,S Ben Baker

doi:10.1038/s41598-020-75169-4

Abstract

The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.

Highlights

The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery
Work previously reported by our co-authors using a solid silicon microarray patch, called the Nanopatch, applied to the skin with a similar applicator system found Microarray patches (MAP) application resulted in an immediate mild erythema and oedema response which lasted for a period of days
Given the potential for MAPs to become the vaccine delivery method of choice, understanding how the MAP itself interacts with the skin is important knowledge

Summary

Introduction

The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. This capability is the result of an evolutionary development of complex protective immune and inflammatory responses to an assortment of common, benign or pronounced, provocations including ultraviolet radiation, toxins, viral or bacterial pathogens and minimal mechanical w ounding[1,2,3,4,5,6,7,8] This protective, inflammatory and immunological capability makes the skin an attractive target for efficient vaccine delivery. Work previously reported by our co-authors using a solid silicon microarray patch, called the Nanopatch, applied to the skin with a similar applicator system found MAP application resulted in an immediate mild erythema and oedema response which lasted for a period of days The focus of these papers was on safety and immunogenicity (in phase 1 influenza trials) and the clinical features associated with use of the MAP13. Our paper seeks to elucidate in detail the various aspects of skin reactivity

Methods

Results

Conclusion